In a high-stakes game of cat-and-mouse, overseas labs are churning out new synthetic drugs at a furious pace, often staying a step ahead of authorities and helping to fuel America’s rampant opioid crisis.

The United Nations Commission on Narcotic Drugs estimates that “new psychoactive substances”—a broad list that includes synthetic opioids—are emerging globally at an average rate of one a week. As with U-47700, rogue chemists sometimes piggyback on research by legitimate scientists that was abandoned before making it to the legal market.

Synthetic opioids are often more deadly than other kinds of common designer drugs, such as artificial cannabinoids or stimulants known as bath salts. Some opioids have flared up before—fentanyl variants caused problems on the West Coast in the late 1970s and 1980s—and they are roaring back at a perilous time.

The designer opioids mainly come from Chinese labs, the DEA says, and many labs sell them openly in online drug bazaars. On online forums, people compare notes on their experiences using the synthetics.

The U.S. surveillance system for these chemicals is a largely informal network of crime labs, medical examiners and law-enforcement authorities who share clues and alert each other when they find something new. It can be a laborious task, slowed in part by the challenge of finding something they didn’t know they were looking for.

At least six states specifically banned U-47700 before the DEA announced plans in September to make the drug illegal. DEA spokesman Rusty Payne said the agency’s scheduling actions are subject to “exhaustive reviews,” which take time.

So far this year through September, NMS Labs, a major private lab outside Philadelphia that works with states around the U.S., has tallied 105 overdose deaths related to U-47700 and 265 fatalities related to furanyl fentanyl—an analog, or chemical compound that is closely related to fentanyl. Axis Forensic Toxicology, a private lab firm in Indianapolis, has seen another 20 deaths linked to U-47700.

The U-47700-related fatalities span at least 31 states from Alaska to Utah to Florida.

The origins of U-47700 date to 1973, when Upjohn Co. asked its scientist Jacob Szmuszkovicz to create a drug with the pain-relieving power of morphine, but without the risk, according to a chapter he wrote for a 1999 book on drug research. Researchers wanted to find the Holy Grail that is elusive to this day: potent pain relievers that don’t have dangerous side effects, such as addiction and a potentially fatal slowdown in breathing.

By about 1974, Dr. Szmuszkovicz created a chemical Upjohn dubbed U-47700 at a company lab in Kalamazoo, Mich. Researchers knew it was a morphine-like drug when it triggered erect tails in mice, a reaction known as a Straub tail, says Phil von Voigtlander, a retired Upjohn research director who worked on the project.

Another test, which involved shining a hot light on mice’s tails to judge how long it took them to move, helped measure U-47700’s potency, says Dr. von Voigtlander. He learned the compound worked on the same receptor as morphine with roughly 7.5 times the strength.

Further rodent testing also revealed a downside. “Once we saw that it just caused tolerance and dependence like opioids and had opioid side effects, we thought, well, that’s just another morphine and that’s not what we’re looking for,” Dr. von Voigtlander says.

He calls U-47700 an important research steppingstone, and Upjohn patented the chemical. The company never tested U-47700 on people.

These kinds of pharmaceutical research efforts leave behind copious patents and scientific papers, which can serve as recipes for today’s enterprising chemists. Some researchers believe Chinese labs are scouring patent literature for new synthetic compounds to produce, before selling them.

Foreign labs began making U-47700 and offering it for sale online by late 2014, according to a forum on the social-media website Reddit devoted to discussion of chemical vendors and frequented by drug users. Buyers can choose from an array of online vendors selling synthetic drugs, including opioids, dubbed “research chemicals.”

The websites typically carry warnings that the chemicals they sell are “not for human consumption”—an attempt to gain legal cover, authorities say—and that buyers are responsible for complying with their home countries’ laws.

U-47700 began claiming lives in the U.S. by May 2015, when a 28-year-old man overdosed in Knox County, Tenn. The medical examiner there initially pegged his death to oxycodone, which was in his system. It took many more months to discover U-47700 was also there.

First, labs had to figure out what the drug was. NMS Labs detected U-47700 in November 2015 while testing blood samples from four different states at its facility outside Philadelphia.

“We actually found it by accident,” says Barry Logan, chief scientist there. U-47700 closely resembles a synthetic opioid called AH-7921—another research relic—which NMS had started watching for last year.

NMS, which is now rushing to create new tests to screen for 21 different designer opioids, eventually linked U-47700 to the Knox County case.

A dangerous strain of heroin with a “Game of Thrones”label has been circulating in Vermont and New Hampshire, where officials have counted nearly a dozen recent overdoses.

Vermont’s Department of Health said the strain of heroin is possibly laced with fentanyl, which makes the drug 50 times stronger. Fentanyl is a powerful opioid that is similar to morphine but is 50 to 100 times more potent, according to the National Institute on Drug Abuse. It’s usually used to treat severe pain.

The heroin bags being passed around bear the logo of the hit HBO show, which may be bolstering its popularity on the streets.

It was also involved in a 32-year-old man’s overdose in New Hampshire.

Although it was a fentanyl overdose that killed Prince April 21, the medical examiner said it was part of a deadly chemical cocktail.

A source close to the investigation says U47700 was part of the mixture. The potent painkiller is a synthetic opioid, eight times stronger than morphine.

Investigative sources told reporter Beth McDonough that Prince may have thought he was taking a legitimate painkiller, like hydrocodone or fentanyl, that unknowingly also had U-47700 in it.

The pills often look just like other medications. Plus, U47700 can be resistent to the life-saving antidote Narcan.

Because U-47700 is not considered a controlled substance by state or federal agents, it's not regulated. The Drug Enforcement Administrations says it tends to be produced overseas in China or Eastern Europe. It's widely available, easily accessible and affordable, about $40 online.

Legal synthetics have caused "upwards of 50 deaths" nationwide during the last four months, according to Barry Logan, director of the Center of Forensic Science and Education. The center is the nonprofit research arm of NMS Labs, which tests for the substances at its Willow Grove headquarters.

NMS confirmed one death in Illinois caused by W-18 and is investigating its role in another.

"The bigger problem right now is the designer opioid U-47700 and the designer fentanyl, furanyl, fentanyl," Logan said, adding that NMS had detected the two substances in a string of fatal overdoses that reached from Florida to Maine.

An epidemic of opioid use has been escalating in recent years, but a potent new painkiller has made a deadly appearance on the streets.

The culprit — fentanyl — is a synthetic pain-relieving drug 50 times more powerful than heroin and 100 times more powerful than morphine.

It can be a lethal killer when laced with its weaker cousin, heroin, or even sold undiluted as heroin itself.

A resurgence in heroin use means Jacksonville’s streets have become a killing field for fentanyl.

It is taking lives in escalating rates from California to Florida. Statistics weren’t even collected on fentanyl deaths as recently at 2014 in this state; but since then its use and its victims have skyrocketed.

“I signed out three (fentanyl-caused death) cases today,” Matthew McMullin, the toxicologist for NMS Labs, which conducts all the toxicological studies for the local medical examiner, said earlier this week.

Two of the bodies were originally suspected to be heroin overdoses but turned out to be fentanyl.

The other person had died due to an overdose caused by fentanyl patches usually used for pain relief. Four patches were on the body when usually one is enough to relieve pain.

W-18 is a synthetic opioid considered to be 10,000 times more powerful than morphine and 100 time stronger than fentanyl—a street drug which caused about 270 overdose deaths last year in the province of Alberta alone.

Four kilograms of a white powder seized by police in the Edmonton area in December 2015 was analysed and turns out to be W-18, a drug that is not yet a controlled substance in Canada.

The quantity is enough to produce millions of tablets, say police. Minute amounts can be deadly. Police are concerned that illicit labs creating tablets may not cut the drug properly and that overdoses will result.

Hospitals have been warned to be on the lookout for drug overdoses and deaths that might be linked to W-18. Dr. Laura Calhoun of the government of Alberta health service joined with police to warn the public: “Our message to the public is this: no matter what drug you use, fentanyl or W-18 may be hiding in it, and they may kill you.”

W-18 is one of thousands of synthetic opiates that is not scheduled as a controlled substance and thus not subject to criminal drug penalties, and one of a handful of drugs that law enforcement officials and scientists say they have seen in increasing numbers in the last six months, as use, abuse and overdose deaths continues to rise.

Another, U-47700, which is seven to eight times stronger than morphine, has been the source of overdoses over the past year in at least 10 states since the first US incident was discovered in Knoxville, Tennessee, in June 2015.

Barry Logan, the executive director for the Center of Forensic Science and Education, said his lab has been able to track down 17 overdose cases of U-47700. And several other overdose deaths and hospitalizations have been identified by local law enforcement in Florida and northern Texas.

The uptick in overdoses and drug seizures involving opiates like W-18 and U-47700 follows actions taken by the Chinese government to criminalize more than 100 chemicals on 1 October 2015, according to Bare.

Once more traditional synthetic drugs were outlawed, chemists looked to more novel substances instead.

The banned chemicals included the makings of acetyl fentanyl, an illicit version or analogue of the powerful prescription painkiller fentanyl that is drastically exacerbating the opioid epidemic in the US. Flakka, a cathinone similar to bath salts, was also banned.

Logan said chemists are finding the recipes for these drugs from research books from the 1970s, when scientists were trying to invent alternatives to morphine.

“In order to find one drug like that you have to test hundreds of them,” said Logan. The result is that there are thousands of variations of research opiates, most of which were never meant to be tried on humans.

Fentanyl, which looks like heroin, is a powerful synthetic painkiller that has been laced into heroin but is increasingly being sold by itself — often without the user’s knowledge. It is up to 50 times more powerful than heroin and up to 100 times more potent than morphine. A tiny bit can be fatal.

In some areas in New England, fentanyl is now killing more people than heroin. In New Hampshire, fentanyl alone killed 158 people last year; heroin killed 32. (Fentanyl was a factor in an additional 120 deaths; heroin contributed to an additional 56.)

Fentanyl represents the latest wave of a rolling drug epidemic that has been fueled by prescription painkillers, as addicts continue to seek higher highs and cheaper fixes.

Nationally, the total number of fentanyl drug seizures reported in 2014 by forensic laboratories jumped to 4,585, from 618 in 2012. More than 80 percent of the seizures in 2014 were concentrated in 10 states: Ohio, followed by Massachusetts, Pennsylvania, Maryland, New Jersey, Kentucky, Virginia, Florida, New Hampshire and Indiana.

It was only last March that the Drug Enforcement Administration issued a nationwide alert about fentanyl, saying that overdoses were “occurring at an alarming rate throughout the United States and represent a significant threat to public health and safety.”

Its chief characteristic is that it is fast acting.

Joanne Peterson, executive director of Learn to Cope, a statewide support network for families involved with addiction, said fentanyl works so quickly that there is often little time to administer naloxone, which reverses the effects of an overdose.

“At least with heroin, there is a chance that if someone relapses, they can get back into recovery,” she said. But with fentanyl, she said, it is only a matter of moments before an addict can be dead.

In recent years there has been a sharp rise in heroin use and heroin overdoses. According to recent data from the National Institute on Drug Abuse (NIDA), a rise in heroin abuse in the United States has been associated with an increase in fatal overdoses. Furthermore, the Substance Abuse and Mental Health Services Administration (SAMHSA) issued an alert about an increase in deaths related to the use of heroin laced with fentanyl.

Fentanyl is a powerful painkiller that is reported to be up to 100 times more potent than morphine, an active ingredient in heroin. Law enforcement from across the country have started to notice that some of the heroin they’ve seized has been laced with the painkiller, fentanyl. Heroin laced with fentanyl is a deadly mixture, especially since most users are unaware that the heroin has been tainted.

This is a significant public health concern. Many users unknowingly inject this potent drug combination and overdose as a result. For those lucky enough to make it to the hospital, treatment may come too little too late. Since most hospitals don’t screen for fentanyl, medical staff may believe that they are only treating a heroin overdose which is usually easier to reverse. More attention needs to be brought to the issue of fentanyl-laced heroin before it becomes a greater epidemic. Additionally, there is evidence that in some cases the heroin being sold is pure fentanyl without any heroin.

In reviewing our results for drug trends, we have found fentanyl to be more prevalent than ever before.

“After seeing the trend of increasing fentanyl use, we knew the best thing to do was to include fentanyl detection to all of our postmortem panels,” Said Dr. Barry Logan, Chief of Forensic Toxicology at NMS Labs.

In just 90 days we saw 88 cases positive for both fentanyl and 6-acetylmorphine (a unique metabolite of heroin) from across the country. You can view a chart of our findings along with a full report here.

The US Drug Enforcement Administration (DEA) voted today (Aug 21) to move forward with rescheduling hydrocodone combination products (HCPs) from schedule III to schedule II drugs. Schedule II medications are considered to be the most potentially harmful and open to abuse.

In addition to containing hydrocodone, HCPs also contain nonnarcotic substances such as aspirin or acetaminophen. Although hydrocodone by itself is classified as a schedule II drug, HCPs have been in the schedule III classification ever since the Controlled Substances Act (CSA) was first passed by Congress back in 1971.

"Based on the consideration of all comments, the scientific and medical evaluation and accompanying recommendation of the HHS,...the DEA finds that these facts and all other relevant data constitute evidence of potential for abuse of HCPs," write the DEA in their final rule.

"As such, the DEA is rescheduling HCPs as a schedule II controlled substance under the CSA," they add.

Substantial Feedback

HCPs are currently approved for marketing for the treatment of pain and for cough suppression.

The DEA published its formal proposal in February and asked for feedback, which could be given until April 28. The organization received 573 comments, of which 52% supported the recommended rescheduling, 41% opposed, and 7% did not voice a definitive opinion.

Patrick Morrisey, the attorney general from West Virginia, the state with the highest per capita rate of prescription drug overdoses in 2013, was among those who wrote in support of the rescheduling.

"This reclassification is not only justified given the high abuse and addiction potential of hydrocodone prescription painkillers, it is necessary to combat the drug abuse epidemic that is destroying so many...communities," wrote Morrisey.

"Rescheduling hydrocodone is one way to help prevent this drug from falling into the wrong hands and will ensure that these drugs are handled with the same precautions as other pain medications, such as oxycodone, hydromorphone, and fentanyl," he added in a release.

Also falling under the schedule II classification are illegal substances, such as methamphetamine and heroin, and prescribed medications, such as dextroamphetamine sulphate (Adderal, Teva Pharmaceuticals).

Once the final rule goes into effect, anybody who handles HCPs will be subject to the CSA's schedule II regulatory controls. This will include "administrative, civil, and criminal sanctions applicable to the manufacture, distribution, dispensing, importing, exporting, engaging in research, conducting instructional activities, and conducting chemical analysis" of these substances.

In addition, any individual who handles or desires to hand HCPs will need to register with the DEA.

The final rule will be published in the Federal Register on August 22, 2014.